OUR RESEARCH

Chronic lung diseases and respiratory infections are among the top five causes of death worldwide (WHO, 2014). A large number of bacterial and viral pathogens can cause respiratory infections and underlying health conditions can increase the susceptibility to or be exacerbated by infections.

Understanding the molecular basis of microbial pathogenicity and host susceptibility is pivotal to design effective antimicrobial therapies and improve patient health.   

Our research focusses on the Gram-negative bacterial pathogen Legionella pneumophila and its relatives. Legionella spp. are ubiquitous environmental bacteria but upon inhalation by humans can cause a severe, potentially fatal pneumonia, called Legionnaires’ disease. Cases occur sporadically; however as L. pneumophila can be transmitted by aerosols, the bacteria also cause large, difficult to control outbreaks as seen in Edinburgh or more recently in New York. Risk factors for Legionella infection include advanced age, smoking, male sex and immune suppression.

Legionella infections are often accompanied by varying extra-pulmonary symptoms and the bacteria are unresponsive to treatment with beta-lactams, first choice antibiotics in the empiric therapy of community-acquired pneumonia (CAP). Because of these characteristics Legionella is considered to belong to the atypical respiratory pathogens, which are difficult to diagnose and account for up to 40% of CAPs. 

Key to human infection is Legionella’s ability to evade degradation in alveolar macrophages, immune cells which are usually deployed to detect and kill invading bacteria. The bacteria succeed in this using a sophisticated protein secretion system, the Dot/Icm type IV secretion system (T4SS), to inject an unprecedented number of more than 350 effector proteins into host cells. Although the individual functions of most of these effectors remain unknown it has become clear that they manipulate host cell signalling to enable Legionella to disarm host cell defences and to instead establish a protective, replication permissive niche, the Legionella-containing vacuole (LCV).

We are interested in all aspects of Legionella biology – from evolution and persistence in the environment to the molecular basis of virulence and susceptibility to infection. Current projects focus in particular on the role of the Dot/Icm T4SS, which is essential for pathogenesis, and its effectors in the evasion of host defences.

Ultimately, we aim to translate our basic research into new preventive hygiene measures to minimize exposure, new diagnostics to improve antimicrobial stewardship in respiratory medicine as well as innovative host-directed therapies to resolve Legionella infections.

If you are interested to learn more about our research, to join or collaborate with us please email me g.schroeder@qub.ac.uk!